Evidence review for antibiotics for bacterial meningitis caused by Listeria monocytogenes

Included studies

A systematic review of the literature was conducted but no studies were identified which were applicable to this review question.

See the literature search strategy in appendix B and study selection flow chart in appendix C.

Excluded studies

Studies not included in this review are listed, and reasons for their exclusion are provided in appendix J.

Included studies

A single economic search was undertaken for all topics included in the scope of this guideline, but no economic studies were identified which were applicable to this review question.

The outcomes that matter most

Bacterial meningitis is associated with high rates of mortality and morbidity, and antibiotics are the mainstay of treatment for bacterial meningitis. Therefore, all-cause mortality and long-term neurological impairment were prioritised as critical outcomes due to the severity of these outcomes. Severe developmental delay was prioritised over functional impairment in children and babies, as it is a more relevant and important outcome for this population. Functional impairment was prioritised as a critical outcome in adults due to the concern about the potential long-term limitations of bacterial meningitis on the ability to carry out certain activities of daily life.

In addition to functional impairment (in children and babies), hearing impairment, serious intervention-related adverse effects, and cerebrospinal fluid (CSF) sterilisation were selected as important outcomes in all age groups as these are relatively common after bacterial meningitis and may be related to antibiotic therapy. Intracranial collections as a complication was also included as an important outcome for adults as this is a rare but severe and life threatening complication of bacterial meningitis that may require prolonged antibiotic treatment.

The quality of the evidence

No studies were identified which were applicable to this review question.

Benefits and harms

No evidence was identified on the effectiveness of antibiotics for the treatment of meningitis caused by Listeria monocytogenes, and the committee agreed that given the absence of evidence the first line treatment recommended by the previous NICE guideline on meningitis (NICE 2010) should be retained. The committee recommended intravenous amoxicillin or ampicillin for 21 days for people with meningitis caused by Listeria monocytogenes. They also recommended that advice from an infection specialist should be sought if people have not recovered after 21 days. The previous guideline recommendation only applied to children younger than 3 months, however the committee agreed that the recommendation could be extended to cover all ages as Listeria monocytogenes is also a common infective organism in older adults and there are additional risk factors for Listeria monocytogenes which are not restricted to extremes of age (pregnancy, malignancy, kidney disease, liver disease, diabetes, alcoholism, and immunocompromising treatment). The committee agreed that there is no evidence that the effectiveness of antibiotics in sterilising the cerebrospinal fluid (CSF) would be different in adults and children. The committee acknowledged that there is some evidence that antibiotics penetrate the CSF of very young children better than in older children and adults because their blood-brain barriers are less intact, but, in the committee’s experience, this difference disappears when the meninges are inflamed; therefore, the committee would expect the antibiotics to penetrate into the CSF equally well regardless of age in people with bacterial meningitis.

The committee also recommended seeking the advice of an infection specialist on the addition of intravenous co-trimoxazole for the first 7 days. The committee agreed that this should not happen routinely as co-trimoxazole can be toxic and has additional monitoring requirements associated with it. However, they agreed that combination therapy can be beneficial, especially where there is a bacteraemic or septic component to the illness, but that it should only be done in consultation with an infection specialist (a microbiologist or infectious diseases specialist) because of the associated risks and monitoring requirements. The committee agreed that although gentamicin is more often used as an addition to amoxicillin in current practice, co-trimoxazole would be more appropriate for older adults due to a significant risk of nephrotoxicity with gentamicin. Where co-trimoxazole is used, the committee agreed that it should only be used during the first stage of treatment such as the first 7 days, as this is when it would be most beneficial, and it would avoid using it longer than necessary due to risks associated with it. The committee noted that this was an off-label use of co-trimoxazole (in January 2024) and doses, frequency, and duration in the BNF (British National Formulary 2023) and BNFC (British National Formulary for Children 2023) for severe infections should be followed.

There was no evidence found on antibiotic use for meningitis caused by Listeria monocytogenes in people with an antibiotic allergy, but the committee agreed it was important to make a recommendation for this population. The committee agreed that clinicians should seek information about the nature of the allergy and advice from an infection specialist before making a treatment decision, particularly for people who are pregnant. The committee acknowledged that it is important that treatment is not delayed; however, they agreed that information about the nature of allergy is often readily available from the patient’s family. Given that amoxicillin and ampicillin are penicillin antibiotics an alternative first line treatment was required. Based on their clinical knowledge and experience, the committee agreed that cephalosporin-induced anaphylaxis is rare. The committee recommended that ceftriaxone or cefotaxime should be considered if the nature of the allergic reaction they get is not severe. They also recommended the addition of cotrimoxazole (for 21 days). This is in line with BNF advice in the case of history of hypersensitivity to penicillin for people with meningitis caused by Listeria monocytogenes. If the allergic reaction is severe, alternatives to ceftriaxone or cefotaxime will be needed. The committee discussed that chloramphenicol is commonly used in the case of severe beta-lactam (penicillin, amoxicillin, or cephalosporin) allergy. Based on clinical knowledge and experience, the committee recommended chloramphenicol (in addition to co-trimoxazole) for people with meningitis caused by Listeria monocytogenes and severe antibiotic allergy.

Given that no evidence was identified for this review the committee discussed including a research recommendation on the effectiveness of antibiotics for the treatment of meningitis caused by Listeria monocytogenes. However, the committee agreed that given this condition is very rare it would be unlikely that a clinical trial would be feasible.

Cost effectiveness and resource use

This review question was not prioritised for economic analysis and therefore the committee made a qualitative assessment of the likely cost-effectiveness of their recommendations. Given the absence of any evidence the committee retained the recommendations made by the previous NICE guideline (NICE 2010) and therefore no significant resource impact is anticipated.

Excluded effectiveness studies

The excluded studies table only lists the studies that were considered and then excluded at the full-text stage for this review (N=5) and not studies (N=187) that were considered and then excluded from the search at the full-text stage as per the PRISMA diagram in Appendix C for the other review questions in the same search.

Table 3

Excluded studies and reasons for their exclusion.

Excluded economic studies

No studies were identified which were applicable to this review question.